For many/most games, there is little practical difference between "U" and "E" roms. Both tend to be ported over in English, and the "E" for Europe seems to mean the United Kingdom more often than not.

Then again, there are sometimes pretty big differences between the varying versions ... the general rule of thumb that I use is if I know little/nothing about the versions, to default with "U" if it's available. I'm American, so that makes sense.

It's not always necessarily the best thing to get the ROM file for the version that was meant for your region, however ... sometimes certain versions can be glitchy (Harvest Moon DS), have portions of storyline/script (even gameplay!) omitted (Final Fantasy IV), and so forth.

Really, if you're worried about it, the best thing you can do is a bit of case-by-case research. Failing that, default to your region. Try to get a copy with a "!" code after the region ... this means that it's a verified good dump.

(U) is USA and usually contains only english language; although sometimes it also has french or spanish

(E) is Europe and usually contains multiple languages, including english

Most of the time, the games are exactly the same with the addition of translations. If you are only interested in english, grab the (U): it is often out first, and can be trimmed to a smaller size than the (E) version.

E's Trace Memory is more loyal to a direct japanese translation. U's has more localization (the name of the game for example)
sometimes E gets bonus things in games to make up for the poor english guys that have to wait so long for it to get translated to the other languages
so far for DS, i can't say much.

I used to go for the (E) versions, being from the UK. But the English in the (E) versions tends to be the same as the English in the (U) versions (i.e. American spellings are still in the E versions, such as humor/humour - US/UK respectively). That's probably not on all games, but most from what I've noticed.

The (U) versions tend to have a smaller file size, a few (U) versions are 32MB while the (E) versions are 64MB (both before trimming). I presume this is because of the extra languages, as opposed to any bug fixes.

I guess it depends on the release dates and the publisher. The language (UK/US differences) tends to be better by some publishers than others.

As I understand, so as not to mimic the American culture of violence, (E) games can't legally include guns but instead are limited to menacing facial expressions, slapfights and in some cases, beer farts as fighting mechanics.